Genetic overlap between psychiatric disorders and neuropsychiatric symptoms in HD

Huntingtons disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in HTT. It is diagnosed following a standardized exam of motor control and often presents with cognitive decline and neuropsychiatric signs and symptoms. Recent studies have indicated genetic loci modifying the age at onset of motor symptoms, and it is therefore of interest to determine whether the neuropsychiatric symptoms in HD are influenced by the same genetic variation that mediates risk for psychiatric disorders in the wider population. This hypothesis was investigated by constructing polygenicrisk scores from large recent genetic associationstudies of psychiatric and neurodegenerative disorders and of intelligence, and testing for association with the presentation of signs and symptoms in a large sample (n=5160) of HD patients. Multiple associations of psychiatric disease polygenicrisk scores were observed with neuropsychiatric and cognitive symptoms in HD, of which the most striking were those between schizophrenia and psychosis in HD. Interestingly, polygenicrisk score for increased intelligence was protective for cognitive decline and apathyin HD. Consistent with previous studies, no associations were seen between polygenicrisk scores for the other major neurodegenerative disorders and neuropsychiatric or cognitive symptoms in HD.